In the US, B-SYNC CAR-T cells eliminated glioma in mice — News-Medical
Scientists at the University of California, San Francisco, US, have developed B-SYNC CAR-T cells that activate only after entering the brain and attack tumor cells. In experiments on mice, the therapy eliminated diffuse midline glioma, a lethal form of childhood brain cancer, News-Medical reports.
Activation in the brain
CAR-T therapy involves modifying immune system T cells so that they recognize proteins on tumor cells and destroy them. B-SYNC uses the synNotch cellular sensor: it responds to brevican, a protein present in brain tissue, and triggers production of the CAR receptor only there.
After activation, the T cells seek cells with the EphA2 or IL13Rα2 proteins, which are present on many tumor cells. The development is intended to work regardless of the presence of EGFRvIII, a mutant protein used as a target in the previous E-SYNC approach. According to the researchers, EGFRvIII is present in about 20% of glioblastomas, and tumors can lose this protein during therapy.
Results in models
The researchers administered B-SYNC intravenously to mice with transplanted human diffuse midline glioma cells. Some of the cells entered the brain, activated and attacked the tumor. At the same time, B-SYNC cells detected outside the brain, including in the blood and spleen, did not produce the CAR receptor.
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With intraventricular administration directly into the brain, the therapy eliminated tumors in all tested mice in two diffuse midline glioma models. Conventional CAR-T cells were unable to control the cancer in these experiments. Nearly seven weeks after treatment, scientists reinjected the animals with glioma cells: all mice that received B-SYNC rejected the new tumors.
Preparing trials
The UCSF team is preparing B-SYNC CAR-T for clinical trials at UCSF Health, which could begin as early as April 2027. During the first trial, they plan to assess different combinations of intravenous and intraventricular administration of the therapy. For repeated intraventricular administrations, patients are expected to receive a shunt connecting the brain ventricles to a reservoir on the scalp.
The study results were published on October 28, 2026, in the journal Science Translational Medicine. Diffuse midline glioma infiltrates the brainstem, which controls breathing, heartbeat and swallowing, and, according to the researchers, children with this diagnosis almost always die within a year of diagnosis.
